The protein chromogranin, which was originally isolated from adrenal chromaffin granules has been found to be a pan-marker for neuroendocrine cells. The proposed experiments aim toward understanding the nature of chromogranin structure and expression. Using cDNA for chromogranin, the number of mRNAs coding for chromogranin will be assessed. The peptide fragments of the various forms of chromogranin will be compared in order to further understand their interrelationships, and to determine the location of proteolytic cleavage sites. Heterogeneity in chromogranin immunostaining, both in tissue sections and in cultured cells will be studied. The relationship of functional status to chromogranin immunoreactivity will also be explored. The time of appearance of chromogranin in development of neuroendocrine tissues will be studied by immunohistochemistry and in situ hybridization. The extent of phosphorylation of membrane and soluble chromogranin will be compared. Incorporation of 32P in chromaffin granules will be measured. The position of phosphorylation sites will be located.